Immune cells from blood attack Alzheimer's plaques

McCaffrey, Pat

doi:10.1016/s1474-4422(06)70398-2

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Combined with the previous reports demonstrating that inflammatory cytokines secreted by activated microglia induce a subtype of reactive astrocytes, termed A1, which induces the death of neurons and oligodendrocytes 69 , our data collectively suggest that YU102 exerts its efficacy via suppression of IL-1α-mediated microglial inflammatory responses. While a relatively minor contribution of peripheral immune cells (macrophages) in AD progression has been also suggested 74 , the impact of YU102 on these cells needs to be verified. LMP2 inhibition alone appears to be sufficient to suppress the secretion of inflammatory cytokines from microglial cells since inhibition of LMP2 but not Y was observed in Tg2576 mice treated with YU102.…”

Section: Discussionmentioning

confidence: 99%

A dual inhibitor of the proteasome catalytic subunits LMP2 and Y attenuates disease progression in mouse models of Alzheimer’s disease

Yeo

Lee

Baek

et al. 2019

Sci Rep

View full text Add to dashboard Cite

The immunoproteasome (iP) is a variant of the constitutive proteasome (cP) that is abundantly expressed in immune cells which can also be induced in somatic cells by cytokines such as TNF-α or IFN-γ. Accumulating evidence support that the iP is closely linked to multiple facets of inflammatory response, eventually leading to the development of several iP inhibitors as potential therapeutic agents for autoimmune diseases. Recent studies also found that the iP is upregulated in reactive glial cells surrounding amyloid β (Aβ) deposits in brains of Alzheimer’s disease (AD) patients, but the role it plays in the pathogenesis of AD remains unclear. In this study, we investigated the effects of several proteasome inhibitors on cognitive function in AD mouse models and found that YU102, a dual inhibitor of the iP catalytic subunit LMP2 and the cP catalytic subunit Y, ameliorates cognitive impairments in AD mouse models without affecting Aβ deposition. The data obtained from our investigation revealed that YU102 suppresses the secretion of inflammatory cytokines from microglial cells. Overall, this study indicates that there may exist a potential link between LMP2/Y and microglia-mediated neuroinflammation and that inhibition of these subunits may offer a new therapeutic strategy for AD.

show abstract

Section: Discussionmentioning

confidence: 99%